As a newly emerged class of anticancer bioagents in the most precise and selectively targeted way, antibody-drug conjugate (ADC) combines the cancer-targeting abilities of monoclonal antibodies with the cytotoxicity potency of payload, delivering highly cytotoxic drug into tumors via 'targeted chemotherapy'. ADC has revolutionized the treatment landscape of human epidermal growth factor receptor 2 positive and triple negative subtypes in breast cancer. Three ADCs have been approved by U. S. Food and Drug Administration with breast cancer indications, including trastuzumab emtansine (T-DM1; also approved in China), trastuzumab deruxtecan (T-DXd, DS-8201) and sacituzumab govitecan (IMMU-132; also approved in China). Antibodies, cytotoxic drug, linker, and conjugation process are implicated in ADC profile, resulting in unique adverse drug reactions and toxicity heterogeneity within ADC class. For example, more attention should be paid to the management of thrombocytopenia, hepatotoxicity, and reductions in left ventricular ejection fraction (LVEF) in patients treated with trastuzumab emtansine; clinical physicians should pay attention to the risk of neutropenia, interstitial lung disease/pneumonitis, and reductions in LVEF when treated with trastuzumab deruxtecan; sacituzumab govitecan most frequently caused neutropenia, anemia and diarrhea requiring close monitor. ADC has generally favorable safety profiles, and dose modifications and/or symptomatic supporting treatment are effective in terms of toxicity management. This consensus aims at providing guidance for clinical oncologists of early detection, regular assessment, timely management and follow-up monitor of ADC-associated adverse reactions/events.
Ado-Trastuzumab Emtansine/therapeutic use* ; Antibodies, Monoclonal/therapeutic use* ; Antineoplastic Agents, Immunological/therapeutic use* ; Breast Neoplasms/therapy* ; Camptothecin/adverse effects* ; Consensus ; Cytotoxins/therapeutic use* ; Female ; Humans ; Immunoconjugates/therapeutic use* ; Neutropenia/etiology* ; Receptor, ErbB-2/metabolism* ; Trastuzumab/therapeutic use* ; Triple Negative Breast Neoplasms/therapy* ; Ventricular Function, Left

OBJECTIVE: To investigate the effect of recombinant human granulocyte colony stimulating factor (rhG-CSF) on the clinical efficacy and flow cytometry (FCM) minimal residual disease (MRD) of patients with acute myeloid leukemia (AML) after initial induction therapy in the real world. METHODS: The clinical data of 44 AML patients who were diagnosed for the first time in the Department of Hematology, The Second Hospital of Anhui Medical University, and received the initial induction therapy were retrospectively analyzed. According to whether rhG-CSF was used after treatment, these patients were divided into control group and therapy group. The complete remission (CR) rate, duration of neutropenia, incidence of infection, duration of fever, cost of antibiotics drugs, length of hospital stay, FCM MRD, and relapse-free survival (RFS) time were compared between the two groups. RESULTS: The CR rate in the control group was 60%, and 74% in the therapy group (P=0.3429). The duration of neutropenia was (21.28±7.91) days in the control group and (14.79±3.07) days in the therapy group (P=0.0016). The duration of fever was (12.80±7.31) days in the control group and (9.11±7.48) days in the therapy group (P=0.0136). While, there were no statistically significant differences between the two groups in the incidence of infection, cost of antibacterial drugs, length of hospital stay and RFS time (all P>0.05). In addition, it is particularly noteworthy that among the patients who finally obtained CR in the therapy group, 66% of them had myeloid precursor cells detected by peripheral blood FCM (accounting for 2.25%±0.99%) at the time of the first release of neutropenia, which was easy to be misdiagnosed as MRD positive. CONCLUSION rhG-CSF not only don't affect the clinical remission rate after the initial induction treatment of AML, but also significantly shortens the time of duration of neutropenia and fever, however, it may affect the analysis of peripheral blood FCM MRD detection results when the neutropenia is released for the first time.
Flow Cytometry ; Granulocyte Colony-Stimulating Factor/therapeutic use* ; Humans ; Induction Chemotherapy/adverse effects* ; Leukemia, Myeloid, Acute/therapy* ; Neoplasm, Residual/etiology* ; Neutropenia ; Recombinant Proteins/therapeutic use* ; Retrospective Studies ; Treatment Outcome

A boy was admitted at the age of 17 months. He had psychomotor retardation in early infancy. Physical examination revealed microcephalus, unusual facies, and a single palmar crease on his right hand, as well as muscle hypotonia in the extremities and hyperextension of the bilateral shoulder and hip joints. Genetic detection identified two pathogenic compound heterozygous mutations, c.8868-1G>A (splicing) and c.11624_11625del (p.V3875Afs*10), in the VPS13B gene, and thus the boy was diagnosed with Cohen syndrome. Cohen syndrome is a rare autosomal recessive disorder caused by the VPS13B gene mutations and has complex clinical manifestations. Its clinical features include microcephalus, unusual facies, neutropenia, and joint hyperextension. VPS13B gene detection helps to make a confirmed diagnosis.
Base Sequence ; Developmental Disabilities ; diagnosis ; genetics ; Fingers ; abnormalities ; Humans ; Infant ; Intellectual Disability ; diagnosis ; genetics ; Male ; Microcephaly ; diagnosis ; genetics ; Muscle Hypotonia ; diagnosis ; genetics ; Mutation ; Myopia ; diagnosis ; genetics ; Neutropenia ; complications ; genetics ; psychology ; Obesity ; diagnosis ; genetics ; Psychomotor Disorders ; diagnosis ; etiology ; genetics ; Retinal Degeneration ; diagnosis ; genetics ; Vesicular Transport Proteins ; genetics

Neutrophils, an important type of human immune cells, are involved in host defense against infections. Neutropenia refers to a group of diseases manifesting as a reduction in the absolute value of mature neutrophils and is often accompanied by an increased risk of bacterial infection. According to etiology and pathogenesis, neutropenia is classified into congenital and acquired neutropenia. This article reviews the current research status and advances in the etiology of neutropenia in children. A deep understanding of the etiology of neutropenia helps to improve the diagnosis and treatment of this disease.
Biomedical Research ; Child ; Humans ; Neutropenia ; classification ; etiology ; therapy

Peripheral T cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with poor prognosis. Elderly (age ≥ 65years) patients generally have impaired bone marrow function, altered drug metabolism, comorbidities, and poor functional status. Thus, treatment of elderly patients with relapsed or refractory PTCL remains a challenge for clinicians. A recent study disclosed that pralatrexate has a synergistic effect in combination with bortezomib. Weekly pralatrexate and bortezomib were administered intravenously for 3 weeks in a 4-week cycle. Of 5 patients, one achieved complete response after 4 cycles which has lasted 12 months until now. Another patient attained partial response after 2 cycles. Only 1 patient experienced grade 3 thrombocytopenia and neutropenia. Two patients suffered from grade 3 mucositis. Combination therapy with pralatrexate and bortezomib may be used as a salvage therapy for relapsed or refractory PTCL in the elderly with a favorable safety profile.
Aged ; Aminopterin/adverse effects/*analogs & derivatives/therapeutic use ; Antineoplastic Agents/adverse effects/*therapeutic use ; Bortezomib/adverse effects/*therapeutic use ; Drug Administration Schedule ; Drug Therapy, Combination ; Humans ; Lymphoma, T-Cell, Peripheral/diagnostic imaging/*drug therapy/pathology ; Male ; Neoplasm Recurrence, Local ; Neutropenia/etiology ; Positron Emission Tomography Computed Tomography

BACKGROUND/AIMS: Chronic hepatitis C (CHC) is a major comorbidity in patients with hemophilia. However, there are no published data on the efficacy of antiviral therapy in Korea. We assessed the safety and efficacy of combination therapy with peginterferon alpha-2a plus ribavirin for CHC in hemophilia. METHODS: Patients (n=115) were enrolled between March 2007 and December 2008. Seventy-seven patients were genotype 1 or 6, and 38 patients were genotype 2 or 3. We evaluated rapid virologic responses (RVRs), early virologic response (EVRs), end-of-treatment response (ETRs), sustained virologic response (SVRs), and relapses. Safety evaluations included adverse events and laboratory tests. RESULTS: Eleven patients were excluded from the study because they had been treated previously. Among the remaining 104 treatment-naive patients, RVR was achieved in 64 (60.6%), ETR was achieved in 95 (91.3%), and SVR was achieved in 89 (85.6%). Relapse occurred in eight patients (8.9%). Common adverse events were hair loss (56.7%) and headache (51.0%). Common hematologic adverse events were neutropenia (22.1%), anemia (27.9%), and thrombocytopenia (3.8%). However, there were no serious adverse events such as bleeding. RVR was the only predictor of SVR in multivariate analysis. CONCLUSIONS: Peginterferon alpha-2a plus ribavirin combination treatment produced a favorable response rate in CHC patients with hemophilia without serious adverse events.
Adult ; Aged ; Antiviral Agents/adverse effects/*therapeutic use ; Drug Therapy, Combination ; Fatigue/etiology ; Female ; Genotype ; Headache/etiology ; Hemophilia A/*complications ; Hepacivirus/genetics ; Hepatitis C, Chronic/complications/*drug therapy/virology ; Humans ; Interferon-alpha/adverse effects/*therapeutic use ; Liver/pathology ; Male ; Middle Aged ; Neutropenia/etiology ; Polyethylene Glycols/adverse effects/*therapeutic use ; RNA, Viral/blood ; Recombinant Proteins/adverse effects/therapeutic use ; Recurrence ; Republic of Korea ; Ribavirin/adverse effects/*therapeutic use ; Treatment Outcome

OBJECTIVETo retrospectively compare the efficacy of postoperative radiotherapy (RT) alone with that of postoperative radiotherapy with concurrent chemotherapy (CRT) for thoracic esophageal squamous cell carcinoma (EPC) with positive lymph nodes, and to evaluate the clinical value of RT + CRT.

METHODS304 EPC patients underwent esophagectomy with three-field lymph node dissection had pathological lymph node metastases, but no hematogenous distant metastasis. Among them, 140 cases underwent postoperative RT alone, and 164 cases underwent postoperative CRT. The dose of irradiation was 50 Gy, and the chemotherapy regimen was taxol and cis-platinum, and a cycle was 21 days.

RESULTSThe 1-, 3- and 5-year total survival rates of the whole group were 90.1%, 56.6% and 43.3%, respectively, with a median survival time of 49.7 months. The 5-year overall survival rates of the CRT and RT groups were 47.4% and 38.6%, respectively (P = 0.030), with a median survival time of 53.5 and 41.7 months, respectively (P = 0.030). The overall survival rates of the patients who underwent 1, 2, 3, 4 cycles of chemotherapy were 24.4%, 53.0%, 58.1% and 43.3%, respectively (P = 0.007). Among them, the 5-year total survival rate of patients with 2-4 cycles of chemotherapy was significantly better than that of patients who underwent one cycle of chemotherapy (P = 0.001). Univariate analysis showed that number of metastatic lymph nodes, pT stage, therapeutic regimen and number of chemotherapy cycles were significantly correlated with the prognosis of the patients (P < 0.05 for all). Multivariate analysis showed that number of metastatic lymph nodes, pT stage, and number of chemotherapy cycles were independent prognostic factors of the patients (P < 0.05 for all). Early toxic effects including neutropenia, radiation esophagitis, and gastrointestinal effects were significantly more severe in the CRT group than that in the RT group (P < 0.05), however, there were no significant differences of late toxic effects between the two groups (P > 0.05).

CONCLUSIONPostoperative CRT for thoracic EPC with positive lymph nodes can improve the survival rate, with tolerable adverse effects.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma, Squamous Cell ; drug therapy ; pathology ; radiotherapy ; surgery ; Chemoradiotherapy ; adverse effects ; Cisplatin ; administration & dosage ; Esophageal Neoplasms ; drug therapy ; pathology ; radiotherapy ; surgery ; Esophagectomy ; Esophagitis ; etiology ; Female ; Follow-Up Studies ; Humans ; Lymph Node Excision ; Lymphatic Irradiation ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Neutropenia ; chemically induced ; etiology ; Paclitaxel ; administration & dosage ; Particle Accelerators ; Postoperative Period ; Retrospective Studies ; Survival Rate

Febrile neutropenia (FN) is the major toxicity of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen in the treatment of diffuse large B-cell lymphoma (DLBCL). The prediction of neutropenia and FN is mandatory to continue the planned R-CHOP therapy resulting in successful anti-cancer treatment. The clinical features and patterns of neutropenia and FN from 181 DLBCL patients treated with R-CHOP were analyzed retrospectively. Sixty percent (60.2%) of patients experienced at least one episode of grade 4 neutropenia. Among them, 42.2% of episodes progressed to FN. Forty-eight percent (48.8%) of patients with FN was experienced their first FN during the first cycle of R-CHOP. All those patients never experienced FN again during the rest cycles of R-CHOP. Female, higher stage, international prognostic index (IPI), age > or =65 yr, comorbidities, bone marrow involvement, and baseline serum albumin < or =3.5 mg/dL were significant risk factors for FN by univariate analysis. Among these variables, comorbidities (P=0.009), bone marrow involvement (P=0.006), and female gender (P=0.024) were independent risk factors for FN based on multivariate analysis. On observing the patterns of neutropenia and FN, primary prophylaxis of granulocyte colony-stimulating factor (G-CSF) and antibiotics should be considered particularly in female patients, patients with comorbidities, or when there is bone marrow involvement of disease.
Adolescent ; Adult ; Age Factors ; Aged ; Antibodies, Monoclonal, Murine-Derived/adverse effects/*therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Chemotherapy-Induced Febrile Neutropenia/*etiology ; Cyclophosphamide/administration & dosage/adverse effects/therapeutic use ; Demography ; Doxorubicin/administration & dosage/adverse effects/therapeutic use ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse/*drug therapy ; Male ; Middle Aged ; Neoplasm Staging ; Neutropenia/etiology/pathology ; Prednisone/administration & dosage/adverse effects/therapeutic use ; Retrospective Studies ; Risk Factors ; Sex Factors ; Vincristine/administration & dosage/adverse effects/therapeutic use ; Young Adult

The application of simultaneous integrated boost-intensity modulated radiotherapy (SIB-IMRT) in pediatric and adolescent nasopharyngeal carcinoma (NPC) is underevaluated. This study aimed to evaluate long-term outcome and late toxicities in pediatric and adolescent NPC after SIB-IMRT combined with chemotherapy. Thirty-four patients (aged 8-20 years) with histologically proven, non-disseminated NPC treated with SIB-IMRT were enrolled in this retrospective study. The disease stage distribution was as follows: stage I, 1 (2.9%); stage III, 14 (41.2%); and stage IV, 19 (55.9%). All patients underwent SIB-IMRT and 30 patients also underwent cisplatin-based chemotherapy. The prescribed dose of IMRT was 64-68 Gy in 29-31 fractions to the nasopharyngeal gross target volume. Within the median follow-up of 52 months (range, 9-111 months), 1 patient (2.9%) experienced local recurrence and 4 (11.8%) developed distant metastasis (to the lung in 3 cases and to multiple organs in 1 case). Four patients (11.8%) died due to recurrence or metastasis. The 5-year locoregional relapse-free survival, distant metastasis-free survival, disease-free survival, and overall survival rates were 97.1%, 88.2%, 85.3%, and 88.2%, respectively. The most common acute toxicities were grades 3-4 hematologic toxicities and stomatitis. Of the 24 patients who survived for more than 2 years, 16 (66.7%) and 15 (62.5%) developed grades 1-2 xerostomia and ototoxicity, respectively. Two patients (8.3%) developed grade 3 ototoxicity; no grade 4 toxicities were observed. SIB-IMRT combined with chemotherapy achieves excellent long-term locoregional control in pediatric and adolescent NPC, with mild incidence of late toxicities. Distant metastasis is the predominant mode of failure.
Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma ; Child ; Cisplatin ; administration & dosage ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Leukopenia ; etiology ; Lung Neoplasms ; secondary ; Male ; Nasopharyngeal Neoplasms ; drug therapy ; pathology ; radiotherapy ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Neutropenia ; etiology ; Radiotherapy Dosage ; Radiotherapy, Intensity-Modulated ; adverse effects ; methods ; Retrospective Studies ; Stomatitis ; etiology ; Survival Rate ; Xerostomia ; etiology ; Young Adult

Neoadjuvant chemotherapy plus radiotherapy is the most common treatment regimen for advanced nasopharyngeal carcinoma (NPC). Whether chronomodulated infusion of chemotherapy can reduce its toxicity is unclear. This study aimed to evaluate the toxic and therapeutic effects of sinusoidal chronomodulated infusion versus flat intermittent infusion of cisplatin (DDP) and 5-fluorouracil (5-FU) followed by radiotherapy in patients with locoregionally advanced NPC. Patients with biopsy-diagnosed untreated stages III and IV NPC (according to the 2002 UICC staging system) were randomized to undergo 2 cycles of sinusoidal chronomodulated infusion (Arm A) or flat intermittent constant rate infusion (Arm B) of DDP and 5-FU followed by radical radiotherapy. Using a "MELODIE" multi-channel programmed pump, the patients were given 12-hour continuous infusions of DDP (20 mg/m2) and 5-FU (750 mg/m2) for 5 days, repeated every 3 weeks for 2 cycles. DDP was administered from 10:00 am to 10:00 pm, and 5-FU was administered from 10:00 pm to 10:00 am each day. Chronomodulated infusion was performed in Arm A, with the peak deliveries of 5-FU at 4:00 am and DDP at 4:00 pm. The patients in Arm B underwent a constant rate of infusion. Radiotherapy was initiated in the fifth week, and both arms were treated with the same radiotherapy techniques and dose fractions. Between June 2004 and June 2006, 125 patients were registered, and 124 were eligible for analysis of response and toxicity. The major toxicity observed during neoadjuvant chemotherapy was neutropenia. The incidence of acute toxicity was similar in both arms. During radiotherapy, the incidence of stomatitis was significantly lower in Arm A than in Arm B (38.1% vs. 59.0%, P = 0.020). No significant differences were observed for other toxicities. The 1-, 3-, and 5-year overall survival rates were 88.9%, 82.4%, and 74.8% for Arm A and 91.8%, 90.2%, and 82.1% for Arm B. The 1-, 3-, and 5-year progression-free survival rates were 91.7%, 88.1%, and 85.2% for Arm A and 100%, 94.5%, and 86.9% for Arm B. The 1-, 3-, and 5-year distant metastasis-free survival rates were 82.5%, 79.1%, and 79.1% for Arm A and 90.2%, 85.2%, and 81.7% for Arm B. Chronochemotherapy significantly reduced stomatitis but was not superior to standard chemotherapy in terms of hematologic toxicities and therapeutic response.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma ; Cisplatin ; administration & dosage ; Disease-Free Survival ; Dose Fractionation ; Drug Chronotherapy ; Female ; Fluorouracil ; administration & dosage ; Humans ; Induction Chemotherapy ; adverse effects ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; drug therapy ; pathology ; radiotherapy ; Neoplasm Staging ; Neutropenia ; chemically induced ; Radiotherapy, High-Energy ; Stomatitis ; etiology ; Survival Rate ; Young Adult